Clinical Trials Register

Summary
EudraCT Number:	2014-002155-25
Sponsor's Protocol Code Number:	TAK-448-2001
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-08-18
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2014-002155-25

A.3

Full title of the trial

An Open-Label, Phase 2a Study to Evaluate the Pharmacodynamics of Different Dosing Regimens of TAK-448, a Kisspeptin Agonist, in Male Overweight/Obese Subjects With Hypogonadotropic Hypogonadism

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Correcting low testosterone levels in men with diabetes: A new treatment approach

A.4.1

Sponsor's protocol code number

TAK-448-2001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Takeda Development Centre Europe Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Takeda Development Centre Europe Ltd
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Takeda Development Centre Europe Ltd
B.5.2	Functional name of contact point	Rudi Taljaard
B.5.3	Address:
B.5.3.1	Street Address	61 Aldwych
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC2B 4AE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+4402031168156
B.5.6	E-mail	rudi.taljaard@takeda.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	TAK-448 0.2 mg/2 mL
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not Yet Known
D.3.9.2	Current sponsor code	TAK-448
D.3.9.3	Other descriptive name	Peptide analog of kisspeptin
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0.3 to 30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hypogonadotropic Hypogonadism

E.1.1.1

Medical condition in easily understood language

Low testosterone levels

E.1.1.2

Therapeutic area

Body processes [G] - Reproductive physiologi cal processes [G08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10021012
E.1.2	Term	Hypogonadotrophic hypogonadism
E.1.2	System Organ Class	100000004860

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the effects on Serum Testosterone(ST) after 4 weeks of SC dose administration, with different doses and dosing frequencies of TAK-448 to overweight/obese subjects with Hypogonadotropic Hypogonadism.

E.2.2

Secondary objectives of the trial

To evaluate pharmacokinetics (PK) of TAK-448 free base form (TAK-448F) after a single SC dose and after 4 weeks of repeated SC dose administration with different doses and dosing frequencies of TAK-448.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
2.The subject or, when applicable, the subject’s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3.The subject has two morning total ST concentrations of ≤12.0 nmol/L ( ≤3.46 ng/mL) taken during the Screening period.
4.The subject is male and aged 18 to 60 years, inclusive.
5.The subject has a body mass index (BMI) between 25.0 and 50.0 kg/m2, inclusive.
6. If diagnosed with T2DM, the subject has a HbA1c concentration <12% at Screening and is on a stable dose of diabetes therapies (including insulin and/or glucagon-like peptide-1 therapies).
7.The subject has a LH concentration <8 IU/L at Screening.
8.A male subject who is nonsterilized* and sexually active with a female partner of childbearing potential* agrees to use adequate contraception* from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.
*Definitions and acceptable methods of contraception are defined in Section 9.1.10 Contraception and Pregnancy Avoidance Procedure and reporting responsibilities are defined in Section 9.1.11 Pregnancy of the protocol.

E.4

Principal exclusion criteria

1.The subject has received any investigational compound within 30 days prior to Screening.
2.The subject has received TAK-448 in a previous clinical study, or previous cohort.
3.The subject is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
4.The subject has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality (other than T2DM, its complications and associated conditions), which may impact the ability of the subject to participate or potentially confound the study results.
5.The subject has a recent history or clinical manifestations of significant CVD – such as a history of myocardial infarction or stroke in the 6 months preceding the Screening visit or has untreated peripheral arterial disease.
6.The subject has a history of hypersensitivity or allergies to any component of the formulation of TAK-448.
7.The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to Screening.
8.The subject is required to take excluded medications, supplements, or food products listed in Section 7.3.
9.The subject intends to donate sperm during the course of this study or for 12 weeks after the last dose of study drug.
10.The subject has clinical evidence of anatomic or pathological hypothalamic/pituitary disease.
11.There is any finding in the subject’s medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-448, or a similar drug in the same class that might interfere with the conduct of the study.
12.The subject has a history of cancer (including prostate cancer), with the exception of basal cell carcinoma which has been in remission for at least 5 years prior to Screening.
13.The subject has a history of or present symptomatic prostate disease (including benign prostatic hyperplasia) or PSA is >4 ng/mL at Screening.
14.The subject has a known history of human immunodeficiency virus infection at Screening.
15.The subject is deemed by the study team to have poor peripheral venous access.
16.The subject has donated or lost 450 mL or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days prior to Screening, or is planning to donate blood for 12 weeks after the last dose of study medication.
17.The subject has a Screening or Day -1 abnormal (clinically significant) ECG. Entry of any subject with an abnormal (not clinically significant) ECG must be approved, and documented by signature of the principal investigator or medically qualified subinvestigator.
18.The subject has abnormal Screening or Day -1 laboratory values that suggest a clinically significant underlying disease or subject with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2× the upper limits of normal (ULN).
19.The subject, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.
20.The subject has had more than two severe hypoglycemic events (requiring third party assistance) within 6 months prior to the Screening Visit.
21.The subject has a diagnosis of type 1 diabetes mellitus.
22.The subject has a history of diabetic ketoacidosis.

E.5 End points

E.5.1

Primary end point(s)

•Percent change from Baseline in area under the effect curve from time 0 to 72 hours (AUEC72) of total ST after 4 weeks of SC dosing with TAK-448 (Day 25 for twice-weekly dosing, Day 22 for once-weekly dosing).
•Percent change from Baseline in AUEC72 of free ST after 4 weeks of SC dosing with TAK 448 (Day 25 for twice-weekly dosing, Day 22 for once-weekly dosing).
•Trough serum concentration (Ctrough defined as lowest Baseline compared to predose of the last dose) of total ST after 4 weeks of SC dosing.
•Ctrough (lowest Baseline compared to predose of the last dose) of free ST after 4 weeks of SC dosing.

E.5.1.1

Timepoint(s) of evaluation of this end point

4 weeks (Day 22 for once - week dosing and or Day 25 for twice-week dosing)

E.5.2

Secondary end point(s)

•Cmax of TAK-448F after first dose (Day 1) and after final dose.
•Area under the plasma concentration time curve of TAK-448F from time 0 to infinity (AUC∞) after first dose (Day 1) and after final dose.
•Area under the plasma concentration-time curve of TAK-448F from time 0 to time of the last quantifiable concentration (AUCt) after first dose (Day 1) and after 4 weeks of dosing.
•Terminal elimination half life (t1/2z) of TAK-448F after single (Day 1) and multiple dose (after 4 weeks of dosing).

E.5.2.1

Timepoint(s) of evaluation of this end point

After first dose (Day 1) and after 4 weeks of dosing (final dose)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

sequential/parallel

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LSLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Thames Valley and South Midlands
G.4.3.4	Network Country	United Kingdom

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-10-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-12-04

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